J Korean Neurosurg Soc.  2022 Sep;65(5):640-651. 10.3340/jkns.2022.0004.

Neuromodulation for Trigeminal Neuralgia

• Chung M
• Huh R

• KMID: 2533027
• DOI: http://doi.org/10.3340/jkns.2022.0004

Abstract

Clinical studies on neuromodulation intervention for trigeminal neuralgia have not yet shown promising results. This might be due to the fact that the pathophysiology of chronic trigeminal neuropathy is not yet fully understood. Chronic trigeminal neuropathy includes trigeminal autonomic neuropathy, painful trigeminal neuropathy, and persistent idiopathic facial pain. This disorder is caused by complex abnormalities in the pain processing system, which is comprised of the affective, emotional, and sensory components, rather than mere abnormal sensation. Therefore, integrative understanding of the pain system is necessary for appropriate neuromodulation of chronic trigeminal neuropathy. The possible neuromodulation targets that participate in complex pain processing are as follows : the ventral posterior medial nucleus, periaqueductal gray, motor cortex, nucleus accumbens, subthalamic nucleus, globus pallidus internus, anterior cingulate cortex, hypothalamus, sphenopalatine ganglion, and occipital nerve. In conclusion, neuromodulation interventions for trigeminal neuralgia is yet to be elucidated; future advancements in this area are required

Keyword

Trigeminal neuralgia; Trigeminal caudal nucleus; Deep brain stimulation; Facial pain

Figure

• 

  Fig. 1. Nociceptive networks related to the trigeminal nucleus. Nociception from the trigeminal nerve enters the central nervous system via trigeminal nucleus caudalis (Ⓐ). This primary sensory nucleus sends nociceptive information to the ventral posterior medial nucleus (VPL, Ⓑ), parabrachial nucleus (PBN, Ⓒ), periaqueductal gray (PAG, Ⓓ), and the centromedian (CM)/parafascicular (PF) nucleus (Ⓕ). The CM/PF projects glutamatergic fibers to the striatum (Ⓖ), and relays polysensory integrative information throughout the entire cortices, especially to the anterior cingulate cortex (Ⓗ), insular cortex, prefrontal cortex, primary sensory cortex, and motor cortex. The anterior cingulate cortex and the prefrontal cortex release efferent to the hypothalamus (Ⓘ) and the amygdala (Ⓙ), which processes affective and emotional aspects of pain. The motor cortex (Ⓚ) projects output signal to the subthalamic nucleus (STN) and the striatum, involving procedural memory formation of the basal ganglia. Output signal from the basal ganglia is relayed via the substantia nigra pars reticulata (SNr) and the globus pallidus internus (GPi) to the thalamic recipient. The hypothalamus regulates the autonomic nervous system via the ventral tegmental area (VTA) and the PAG. The PAG releases descending signals for pain modulation (broken arrows) to the nucleus raphe magnus (NRM, Ⓔ), which in turn modulates the trigeminal nucleus caudalis. The amygdala also participates descending pain modulation via locus coeruleus (LC) to the trigeminal nucleus caudalis. VPM : ventral posterior medial.

Reference

References

1. Abdallat M, Saryyeva A, Blahak C, Wolf ME, Weigel R, Loher TJ, et al. Centromedian-parafascicular and somatosensory thalamic deep brain stimulation for treatment of chronic neuropathic pain: a contemporary series of 40 patients. Biomedicines. 9:731. 2021.

2. Adams JE. Naloxone reversal of analgesia produced by brain stimulation in the human. Pain. 2:161–166. 1976.

3. Baldo BA. Prefrontal cortical opioids and dysregulated motivation: a network hypothesis. Trends Neurosci. 39:366–377. 2016.

4. Bálint E, Csillag A. Nucleus accumbens subregions: hodological and immunohistochemical study in the domestic chick (gallus domesticus). Cell Tissue Res. 327:221–230. 2007.

5. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 139:267–284. 2009.

6. Basbaum AI, Fields HL. Endogenous pain control mechanisms: review and hypothesis. Ann Neurol. 4:451–462. 1978.

7. Ben-Haim S, Mirzadeh Z, Rosenberg WS. Deep brain stimulation for intractable neuropathic facial pain. Neurosurg Focus. 45:E15. 2018.

8. Bendtsen L, Zakrzewska JM, Heinskou TB, Hodaie M, Leal PRL, Nurmikko T, et al. Advances in diagnosis, classification, pathophysiology, and management of trigeminal neuralgia. Lancet Neurol. 19:784–796. 2020.

9. Berridge KC, Kringelbach ML. Pleasure systems in the brain. Neuron. 86:646–664. 2015.

10. Blake P, Burstein R. Emerging evidence of occipital nerve compression in unremitting head and neck pain. J Headache Pain. 20:76. 2019.

11. Boivie J, Meyerson BA. A correlative anatomical and clinical study of pain suppression by deep brain stimulation. Pain. 13:113–126. 1982.

12. Burchiel KJ, Raslan AM. Contemporary concepts of pain surgery. J Neurosurg. 130:1039–1049. 2019.

13. Bushnell MC, Ceko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci. 14:502–511. 2013.

14. Calzavara R, Mailly P, Haber SN. Relationship between the corticostriatal terminals from areas 9 and 46, and those from area 8a, dorsal and rostral premotor cortex and area 24c: an anatomical substrate for cognition to action. Eur J Neurosci. 26:2005–2024. 2007.

15. Cappon D, Ryterska A, Lagrata S, Miller S, Akram H, Hyam J, et al. Ventral tegmental area deep brain stimulation for chronic cluster headache: effects on cognition, mood, pain report behaviour and quality of life. Cephalalgia. 39:1099–1110. 2019.

16. Chiang MC, Bowen A, Schier LA, Tupone D, Uddin O, Heinricher MM. Parabrachial complex: a hub for pain and aversion. J Neurosci. 39:8225–8230. 2019.

17. Chung M, Huh R. Different clinical course of pallidal deep brain stimulation for phasic- and tonic-type cervical dystonia. Acta Neurochir (Wien). 158:171–180. 2016.

18. Clelland CD, Zheng Z, Kim W, Bari A, Pouratian N. Common cerebral networks associated with distinct deep brain stimulation targets for cluster headache. Cephalalgia. 34:224–230. 2014.

19. Coffey RJ. Deep brain stimulation for chronic pain: results of two multicenter trials and a structured review. Pain Med. 2:183–192. 2001.

20. Cruccu G, Di Stefano G, Truini A. Trigeminal neuralgia. N Engl J Med. 383:754–762. 2020.

21. Ebel H, Rust D, Tronnier V, Böker D, Kunze S. Chronic precentral stimulation in trigeminal neuropathic pain. Acta Neurochir (Wien). 138:1300–1306. 1996.

22. Ferbinteanu J. Memory systems 2018 - towards a new paradigm. Neurobiol Learn Mem. 157:61–78. 2019.

23. Fontaine D, Bozzolo E, Chivoret N, Paquis P, Lanteri-Minet M. Salvage treatment of trigeminal neuralgia by occipital nerve stimulation. Cephalalgia. 34:307–310. 2014.

24. French JD, Verzeano M, Magoun HW. An extralemniscal sensory system in the brain. AMA Arch Neurol Psychiatry. 69:505–518. 1953.

25. Fuller PM, Sherman D, Pedersen NP, Saper CB, Lu J. Reassessment of the structural basis of the ascending arousal system. J Comp Neurol. 519:933–956. 2011.

26. Godfrey N, Borgland SL. Diversity in the lateral hypothalamic input to the ventral tegmental area. Neuropharmacology. 154:4–12. 2019.

27. Gouveia FV, Hamani C, Fonoff ET, Brentani H, Alho EJL, De Morais RMCB, et al. Amygdala and hypothalamus: historical overview with focus on aggression. Neurosurgery. 85:11–30. 2019.

28. Gruber D, Südmeyer M, Deuschl G, Falk D, Krauss JK, Mueller J, et al. Neurostimulation in tardive dystonia/dyskinesia: a delayed start, sham stimulation-controlled randomized trial. Brain Stimul. 11:1368–1377. 2018.

29. Hamani C, Fonoff ET, Parravano DC, Silva VA, Galhardoni R, Monaco BA, et al. Motor cortex stimulation for chronic neuropathic pain: results of a double-blind randomized study. Brain. 144:2994–3004. 2021.

30. Hosobuchi Y, Adams JE, Rutkin B. Chronic thalamic stimulation for the control of facial anesthesia dolorosa. Arch Neurol. 29:158–161. 1973.

31. Hosobuchi Y, Rossier J, Bloom FE, Guillemin R. Stimulation of human periaqueductal gray for pain relief increases immunoreactive beta-endorphin in ventricular fluid. Science. 203:279–281. 1979.

32. Huh R, Song IU, Chung M. Neuropsychological consequences of pallidal deep brain stimulation altering brain networks. J Clin Neurosci. 54:50–56. 2018.

33. Ilyas A, Pizarro D, Romeo AK, Riley KO, Pati S. The centromedian nucleus: anatomy, physiology, and clinical implications. J Clin Neurosci. 63:1–7. 2019.

34. Keifer OP Jr, Diaz A, Campbell M, Bezchlibnyk YB, Boulis NM. Occipital nerve stimulation for the treatment of refractory occipital neuralgia: a case series. World Neurosurg. 105:599–604. 2017.

35. Khan S, Schoenen J, Ashina M. Sphenopalatine ganglion neuromodulation in migraine: what is the rationale? Cephalalgia. 34:382–391. 2014.

36. Kim HJ, Paek SH, Kim JY, Lee JY, Lim YH, Kim MR, et al. Chronic subthalamic deep brain stimulation improves pain in parkinson disease. J Neurol. 255:1889–1894. 2008.

37. Krüger MT, Avecillas-Chasin JM, Heran MKS, Naseri Y, Sandhu MK, Polyhronopoulos NE, et al. Directional deep brain stimulation can target the thalamic "sweet spot" for improving neuropathic dental pain. Oper Neurosurg (Hagerstown). 21:81–86. 2021.

38. Kumar K, Toth C, Nath RK. Deep brain stimulation for intractable pain: a 15-year experience. Neurosurgery. 40:736–746. 1997.

39. Lai HY, Younce JR, Albaugh DL, Kao YC, Shih YY. Functional MRI reveals frequency-dependent responses during deep brain stimulation at the subthalamic nucleus or internal globus pallidus. Neuroimage. 84:11–18. 2014.

40. Láinez MJ, Marti AS. Sphenopalatine ganglion stimulation in cluster headache and other types of headache. Cephalalgia. 36:1149–1155. 2016.

41. Leone M, Proietti Cecchini A. Deep brain stimulation in headache. Cephalalgia. 36:1143–1148. 2016.

42. Levi V, Cordella R, D'Ammando A, Tringali G, Dones I, Messina G, et al. Dorsal anterior cingulate cortex (ACC) deep brain stimulation (DBS): a promising surgical option for the treatment of refractory thalamic pain syndrome (TPS). Acta Neurochir (Wien). 161:1579–1588. 2019.

43. Levy R, Deer TR, Henderson J. Intracranial neurostimulation for pain control: a review. Pain Physician. 13:157–165. 2010.

44. Levy RM, Lamb S, Adams JE. Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature. Neurosurgery. 21:885–893. 1987.

45. Maarbjerg S, Di Stefano G, Bendtsen L, Cruccu G. Trigeminal neuralgia - diagnosis and treatment. Cephalalgia. 37:648–657. 2017.

46. Mallory GW, Abulseoud O, Hwang SC, Gorman DA, Stead SM, Klassen BT, et al. The nucleus accumbens as a potential target for central poststroke pain. Mayo Clin Proc. 87:1025–1031. 2012.

47. Marchand S, Kupers RC, Bushnell CM, Duncan GH. Analgesic and placebo effects of thalamic stimulation. Pain. 105:481–488. 2003.

48. Marques A, Chassin O, Morand D, Pereira B, Debilly B, Derost P, et al. Central pain modulation after subthalamic nucleus stimulation: a crossover randomized trial. Neurology. 81:633–640. 2013.

49. Mazars GJ. Intermittent stimulation of nucleus ventralis posterolateralis for intractable pain. Surg Neurol. 4:93–95. 1975.

50. Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 150:971–979. 1965.

51. Meyerson BA, Lindblom U, Linderoth B, Lind G, Herregodts P. Motor cortex stimulation as treatment of trigeminal neuropathic pain. Acta Neurochir Suppl (Wien). 58:150–153. 1993.

52. Miller S, Watkins L, Matharu M. Treatment of intractable chronic cluster headache by occipital nerve stimulation: a cohort of 51 patients. Eur J Neurol. 24:381–390. 2017.

53. Moro E, Piboolnurak P, Arenovich T, Hung SW, Poon YY, Lozano AM. Pallidal stimulation in cervical dystonia: clinical implications of acute changes in stimulation parameters. Eur J Neurol. 16:506–512. 2009.

54. Nandi D, Aziz T, Carter H, Stein J. Thalamic field potentials in chronic central pain treated by periventricular gray stimulation -- a series of eight cases. Pain. 101:97–107. 2003.

55. Ossipov MH, Dussor GO, Porreca F. Central modulation of pain. J Clin Invest. 120:3779–3787. 2010.

56. Parent A, Hazrati LN. Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop. Brain Res Brain Res Rev. 20:91–127. 1995.

57. Parmar M, Sharma N, Modgill V, Naidu P. Comparative evaluation of surgical procedures for trigeminal neuralgia. J Maxillofac Oral Surg. 12:400–409. 2013.

58. Pereira EA, Aziz TZ. Neuropathic pain and deep brain stimulation. Neurotherapeutics. 11:496–507. 2014.

59. Pereira EA, Green AL, Aziz TZ. Deep brain stimulation for pain. Handb Clin Neurol. 116:277–294. 2013.

60. Rapisarda A, Ioannoni E, Izzo A, Montano N. What are the results and the prognostic factors of motor cortex stimulation in patients with facial pain? A systematic review of the literature. Eur Neurol. 84:151–156. 2021.

61. Rasskazoff SY, Slavin KV. Neuromodulation for cephalgias. Surg Neurol Int. 4:S136–S150. 2013.

62. Reynolds DV. Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science. 164:444–445. 1969.

63. Richardson DE, Akil H. Pain reduction by electrical brain stimulation in man. Part 1: acute administration in periaqueductal and periventricular sites. J Neurosurg. 47:178–183. 1977.

64. Sadikot AF, Rymar VV. The primate centromedian-parafascicular complex: anatomical organization with a note on neuromodulation. Brain Res Bull. 78:122–130. 2009.

65. Schjerling L, Hjermind LE, Jespersen B, Madsen FF, Brennum J, Jensen SR, et al. A randomized double-blind crossover trial comparing subthalamic and pallidal deep brain stimulation for dystonia. J Neurosurg. 119:1537–1545. 2013.

66. Schmahmann JD, Pandya DN. Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems. Cortex. 44:1037–1066. 2008.

67. Schoenen J, Jensen RH, Lantéri-Minet M, Láinez MJ, Gaul C, Goodman AM, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 33:816–830. 2013.

68. Sewards TV, Sewards MA. The medial pain system: neural representations of the motivational aspect of pain. Brain Res Bull. 59:163–180. 2002.

69. Shephard MK, Macgregor EA, Zakrzewska JM. Orofacial pain: a guide for the headache physician. Headache. 54:22–39. 2014.

70. Shulman R, Turnbull IM, Diewold P. Psychiatric aspects of thalamic stimulation for neuropathic pain. Pain. 13:127–135. 1982.

71. Sims-Williams HP, Javed S, Pickering AE, Patel NK. Characterising the analgesic effect of different targets for deep brain stimulation in trigeminal anaesthesia dolorosa. Stereotact Funct Neurosurg. 94:174–181. 2016.

72. Smith Y, Raju DV, Pare JF, Sidibe M. The thalamostriatal system: a highly specific network of the basal ganglia circuitry. Trends Neurosci. 27:520–527. 2004.

73. Spina A, Mortini P, Alemanno F, Houdayer E, Iannaccone S. Trigeminal neuralgia: toward a multimodal approach. World Neurosurg. 103:220–230. 2017.

74. Stuber GD, Britt JP, Bonci A. Optogenetic modulation of neural circuits that underlie reward seeking. Biol Psychiatry. 71:1061–1067. 2012.

75. Tepper SJ, Stillman MJ. Cluster headache: potential options for medically refractory patients (when all else fails). Headache. 53:1183–1190. 2013.

76. Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T, Koyama S. Chronic motor cortex stimulation for the treatment of central pain. Acta Neurochir Suppl (Wien). 52:137–139. 1991.

77. Varela C. Thalamic neuromodulation and its implications for executive networks. Front Neural Circuits. 8:69. 2014.

78. Venkatraman A, Edlow BL, Immordino-Yang MH. The brainstem in emotion: a review. Front Neuroanat. 11:15. 2017.

79. Vogt BA. Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci. 6:533–544. 2005.

80. Vukovic Cvetkovic V, Jensen RH. Neurostimulation for the treatment of chronic migraine and cluster headache. Acta Neurol Scand. 139:4–17. 2019.

81. Weber K. Neuromodulation and devices in trigeminal neuralgia. Headache. 57:1648–1653. 2017.

82. Weigel R, Krauss JK. Center median-parafascicular complex and pain control. Review from a neurosurgical perspective. Stereotact Funct Neurosurg. 82:115–126. 2004.

83. Wiech K. Deconstructing the sensation of pain: the influence of cognitive processes on pain perception. Science. 354:584–587. 2016.

84. William A, Azad TD, Brecher E, Cherry T, Bernstein I, Bruce DM, et al. Trigeminal and sphenopalatine ganglion stimulation for intractable craniofacial pain--case series and literature review. Acta Neurochir (Wien). 158:513–520. 2016.

85. Young RF, Kroening R, Fulton W, Feldman RA, Chambi I. Electrical stimulation of the brain in treatment of chronic pain. Experience over 5 years. J Neurosurg. 62:389–396. 1985.